The test-negative design (TND) has become a standard approach for vaccine effectiveness (VE) studies. However, previous studies suggested that it may be more vulnerable than other designs to misclassification of disease outcome caused by imperfect diagnostic tests. This could be a particular limitation in VE studies where simple tests (e.g. rapid influenza diagnostic tests) are used for logistical convenience. To address this issue, we derived a mathematical representation of the TND with imperfect tests, then developed a bias correction framework for possible misclassification. TND studies usually include multiple covariates other than vaccine history to adjust for potential confounders; our methods can also address multivariate analyses and be easily coupled with existing estimation tools. We validated the performance of these methods using simulations of common scenarios for vaccine efficacy and were able to obtain unbiased estimates in a variety of parameter settings.

Light gradients are an inherent feature in aquatic ecosystems and play a key role in shaping the biology of phytoplankton. Parasitism by chytrid fungi is gaining increasing attention as a major control agent of phytoplankton due to its previously overlooked ubiquity, and profound ecological and evolutionary consequences. Despite this interest, if and how light conditions modulate phytoplankton chytridiomycosis remains poorly studied. We investigated life-history traits of a chytrid parasite, Rhizophydium megarrhizum, under different light intensities and spectral compositions when infecting two closely related planktonic cyanobacteria with different light-harvesting strategies: Planktothrix rubescens and P. agardhii. In general, parasite transmission was highest under light conditions (both intensity and quality) that maximized growth rates for uninfected cyanobacteria. Chytrid encystment on hosts was significantly affected by light intensity and host strain identity. This likely resulted from higher irradiances stimulating the increased discharge of photosynthetic by-products, which drive parasite chemotaxis, and from strain-specific differences at the cell-surface. Comparisons of parasite transmission and host growth rates under different light conditions suggest the potential for epidemic development at higher irradiances, whereas host and parasite could coexist without epidemic outbreaks at lower light levels. These results illustrate the close relationship between parasite transmission and host fitness, which is ultimately modulated by the external environment.

Social phobia (SP) has onset during early adolescence, and is associated with significant impairment in social and educational functioning of adolescents. Therefore, valid and easy-to-use tools for screening and identification of SP among adolescent community populations are needed. We investigated both construct and discriminative validity, and screening properties of the 17-item Social Phobia Inventory (SPIN) relative to SP diagnoses based on a semi-structured clinical interview (K-SADS-PL), in a sample of 752 12 to 17-year-old Finnish students from general population. The SPIN demonstrated good properties to differentiate adolescents with SP and those with sub-clinical SP symptoms (SSP), from adolescents without SP. The SPIN also differentiated adolescents with SP from those with depressive and disruptive disorders. In this sample 27% of participants scored above the previously suggested SPIN cut-off (15 points) for adolescent SP. We suggest using a somewhat higher cut-off score, 24 points, when using the SPIN as a screen for SP in general adolescent populations. This cut-off score resulted in a sensitivity of 81.2%, a specificity of 85.1%, a positive predictive value of 26.9%, and a negative predictive value of 98.6% in relation to the SP diagnosis in our sample. To screen for both SP and SSP, 19 points as a cut-off score produced satisfactory diagnostic efficiency statistics. The SPIN appears to have good properties for screening and identification of adolescent SP.

Barteria fistulosa and B. dewevrei, central African rain-forest trees, provide nesting cavities for Tetraponera aethiops and T. latifrons ants, respectively, which protect them against herbivores. To compare protection efficiency between these two symbioses, for 20 plants of each species in two sites in Gabon we measured the time elapsed before ants reached a focal leaf, for host leaves that were undisturbed, damaged (cut with scissors) or subjected to slight vibration (mimicking such damage), and for damaged leaves of the non-host Barteria species. Tetraponera aethiops displayed stronger protective behaviour than did T. latifrons. Time to reach a damaged host leaf (4.5 ± 2.6 min, mean ± SD) did not differ significantly from time to reach a leaf subjected to slight vibration (5.2 ± 3.0 min) for T. aethiops, but response to a leaf subjected to slight vibration (9.5 ± 1.9 min) was significantly slower than that to a damaged leaf (7.8 ± 1.9 min) for T. latifrons. The faster response of T. aethiops to slight vibration may have masked a response of this species to chemical signalling. Both ants reached damaged host leaves faster than damaged leaves of the non-host Barteria sp., indicating host plant specificity in ant responses.

Vascular surgery patients are nutritionally vulnerable. Various malnutrition screening and assessment tools are available; however, none has been developed or validated in vascular patients. The present study aimed to: (1) investigate the validity of four commonly administered malnutrition screening tools (Malnutrition Screening Tool (MST), Malnutrition Universal Screening Tool (MUST), Nutrition Risk Screen-2002 (NRS-2002) and the Mini-Nutritional Assessment – Short Form (MNA-SF) and an assessment tool (the Patient-Generated Subjective Global Assessment (PG-SGA)) compared against a comprehensive dietitian’s assessment and (2) evaluate the ability of the instruments to predict outcomes. Vascular inpatients were screened using the four malnutrition screening tools and assessed using the PG-SGA. Each was assessed by a dietitian incorporating nutritional biochemistry, anthropometry and changes in dietary intake. Diagnostic accuracy, consistency and predictive ability were determined. A total of 322 (69·3 % male) patients participated, with 75 % having at least one parameter indicating nutritional deficits. No instrument achieved the a priori levels for sensitivity (14·9–52·5 %). Neither tool predicted EuroQoL 5-dimension 5-level score. All tools except the MNA-SF were associated with length of stay (LOS); however, the direction varied with increased risk of malnutrition on the MUST and NRS-2002 being associated with shorter LOS (P=0·029 and 0·045) and the reverse with the MST and PG-SGA (P=0·005 and <0·001). The NRS-2002 was associated with increased risk of complications (P=0·039). The MST, NRS-2002 and PG-SGA were predictive of discharge to an institution (P=0·004, 0·005 and 0·003). The tools studied were unable to identify the high prevalence of undernutrition; hence, vascular disease-specific screening and/or assessment tools are warranted.

The performance of a new point-of-care diagnostic (Mastatest), an on-farm test designed to identify bacteria and provide antibiotic sensitivity testing information from milk samples, was compared with standard microbiological culture methods. A total of 292 milk samples from clinical mastitis cases in dairy cows on New Zealand dairy farms were examined, and latent class analysis was used to estimate the performance characteristics of both tests. Two hundred and fifty-six samples (87.7%) demonstrated bacterial infection in standard culture, and 269 (92.1%) using the point-of-care diagnostic. The most common bacterial species detected was Streptococcus uberis, found in 195 samples (66.8%) using standard culture and 190 samples (65.1%) using the point-of-care diagnostic. Latent class analysis found no significant differences in test characteristics between the point-of-care diagnostic and standard culture. The estimated sensitivity and specificity of the point-of-care diagnostic against all targets combined were 94.6 and 72.1% respectively; the corresponding estimates for standard culture were 90.5 and 73.9%. Comparison of antibiotic susceptibility testing using the point-of-care diagnostic and the reference method showed similar trends and, in some cases, identical MIC50 and MIC90 values, with at most one antibiotic dilution difference.

Understanding how individual parasite traits contribute to overall fitness, and how they are modulated by both external and host environment, is crucial for predicting disease outcome. Fungal (chytrid) parasites of phytoplankton are important yet poorly studied pathogens with the potential to modulate the abundance and composition of phytoplankton communities and to drive their evolution. Here, we studied life-history traits of a chytrid parasite infecting the planktonic, bloom-forming cyanobacterium Planktothrix spp. under host genotype and thermal variation. When expressing parasite fitness in terms of transmission success, disease outcome was largely modulated by temperature alone. Yet, a closer examination of individual parasite traits linked to different infection phases, such as (i) the establishment of the infection (i.e. intensity of infection) and (ii) the exploitation of host resources (i.e. size of reproductive structures and propagules), revealed differential host genotype and temperature × host genotype modulation, respectively. This illustrates how parasite fitness results from the interplay of individual parasite traits that are differentially controlled by host and external environment, and stresses the importance of combining multiple traits to gain insights into underlying infection mechanisms.

The Bipolar Spectrum Diagnostic Scale (BSDS) is widely validated and used as a screening tool for bipolar disorder. However, there is no BSDS validated version for its use in Mexican population. The aim of the present study was to examine the BSDS diagnostic capacity, and to evaluate its criterion validity and internal consistency for its use in Mexican psychiatric patients. We recruited 200 patients who attended the psychiatric outpatient service of a Mental Health Specialized Hospital and were screened for bipolar disorder using BSDS. To determine the cut-off point, sensitivity and specificity, we used the SCID–I diagnosis as the gold standard in 100 participants with bipolar disorder and 100 with major depression. Internal consistency according to Cronbach’s coefficient alpha was .81. The area under ROC curve for the overall discriminability of BSDS against the criterion of SCID–I for bipolar disorder was .90. Finally, a cut-off value of 12 reached the most stable sensitivity and specificity, with predictive powers higher than .80. In conclusion, the properties of the scale including internal consistency, sensitivity and specificity, make of BSDS a valuable instrument for screening bipolar disorder in Mexican psychiatric population.